Notch Signaling in Central Nervous System: From Cellular Development to Multiple Sclerosis Disease.

INTRODUCTION/OBJECTIVE: Multiple sclerosis (MS), is characterized by autoimmune-driven neuroinflammation, axonal degeneration, and demyelination. This study aimed to explore the therapeutic potential of targeting Notch signaling within the central nervous system (CNS) in the context of MS. Understanding the intricate roles of Notch signaling could pave the way for targeted interventions to mitigate MS progression. METHODS: A comprehensive literature review was conducted using databases such as PubMed, Web of Science, and Scopus. Keywords such as "Notch signaling," "neuroglial interactions," and "MS" were used. The selection criteria included relevance to neuroglial interactions, peer-reviewed publications, and studies involving animal models of MS. RESULTS: This review highlights the diverse functions of Notch signaling in CNS development, including its regulation of neural stem cell differentiation into neurons, astrocytes, and oligodendrocytes. In the context of MS, Notch signaling has emerged as a promising therapeutic target, exhibiting positive impacts on neuroprotection and remyelination. However, its intricate nature within the CNS necessitates precise modulation for therapeutic efficacy. CONCLUSION: This study provides a comprehensive overview of the potential therapeutic role of Notch signaling in MS. The findings underscore the significance of Notch modulation for neuroprotection and remyelination, emphasizing the need for precision in therapeutic interventions. Further research is imperative to elucidate the specific underlying mechanisms involved, which will provide a foundation for targeted therapeutic strategies for the management of MS and related neurodegenerative disorders.

AMP-activated protein kinase as a mediator of mitochondrial dysfunction of multiple sclerosis in animal models: A systematic review.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) disorder characterized by demyelination, neuronal damage, and oligodendrocyte depletion. Reliable biomarkers are essential for early diagnosis and disease management. Emerging research highlights the role of mitochondrial dysfunction and oxidative stress in CNS disorders, including MS, in which mitochondria are central to the degenerative process. Adenosine monophosphate-activated protein kinase (AMPK) regulates the mitochondrial energy balance and initiates responses in neurodegenerative conditions. This systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aimed to comprehensively assess the literature on AMPK pathways, mitochondrial dysfunction, and in vivo studies using MS animal models. The search strategy involved the use of AMPK syntaxes, MS syntaxes, and animal model syntaxes. The PubMed, Scopus, Web of Science, and Google Scholar databases were systematically searched on August 26, 2023 without publication year restrictions. The review identified and analyzed relevant papers to provide a comprehensive overview of the current state of related research. Eight studies utilizing various interventions and methodological approaches were included. Risk of bias assessment revealed some areas of low risk but lacked explicit reporting in others. These studies collectively revealed a complex relationship between AMPK, mitochondrial dysfunction, and MS pathogenesis, with both cuprizone and experimental autoimmune encephalomyelitis models demonstrating associations between AMPK and mitochondrial disorders, including oxidative stress and impaired expression of mitochondrial genes. These studies illuminate the multifaceted role of AMPK in MS animal models, involving energy metabolism, inflammatory processes, oxidative stress, and gene regulation leading to mitochondrial dysfunction. However, unanswered questions about its mechanisms and clinical applications underscore the need for further research to fully harness its potential in addressing MS-related mitochondrial dysfunction.

Screening for causative mutations in ovine BMPR1B and BMP15 genes and their homologous fragments in human.

PURPOSE: The BMPR1B and BMP15 genes are well known for their considerable associations with prolificacy in sheep. These genes may also affect fertility or prolificacy in other species, including human. This study was conducted to investigate possible causative mutations in BMPR1B and BMP15 genes in human and an indigenous breed of sheep. METHODS: Blood samples were collected from 83 singleton- and prolific Mehraban ewes and 81 infertile, singleton- and twin-bearing women. A 190-bp fragment, containing the FecB mutation in ovine BMPR1B, a 380-bp fragment in ovine BMP15 gene and their homologous fragments in human were amplified and then investigated by single-stranded conformation polymorphism and DNA sequencing methods. RESULTS: The FecB mutation of BMPR1B (g.159A>G) was detected in the sheep population, but no polymorphic loci were found in the homologous fragment in studied human samples. The studied fragments of BMP15 were monomorphic in both sheep and human samples. A total of nine and 69 point-differences in the studied fragments of BMPR1B and BMP15 genes were detected between the species, respectively. In sheep, the G allele of BMPR1B had a positive effect on litter size (p<0.05), whereby all AG or GG ewes were prolific. CONCLUSION: The FecB mutation for the first time was detected in Mehraban sheep and therefore could be considered for marker-assisted selection in this breed. The studied fragments of BMPR1B and BMP15 genes are not responsible for reproduction variation in human. More studies on other genes, associated with fertility in human, are necessary in the future.

The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs.

Understanding the transmission pathways of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will aid in developing effective therapies directed at the virus's life cycle or its side effects. While severe respiratory distress is the most common symptom of a coronavirus 2019 (COVID-19) infection, the virus is also known to cause damage to almost every major organ and system in the body. However, it is not obvious whether pathological changes in extra-respiratory organs are caused by direct infection, indirect, or combination of these effects. In this narrative review, we first elaborate on the characteristics of SARS-CoV-2, followed by the mechanisms of this virus on various organs such as brain, eye, and olfactory nerve and different systems such as the endocrine and gastrointestinal systems.

Mitochondrial dysfunction and inflammasome activation in neurodegenerative diseases: Mechanisms and therapeutic implications.

Impaired mitochondrial function is crucial to the pathogenesis of several neurodegenerative diseases. It causes the release of mitochondrial DNA (mtDNA), mitochondrial reactive oxygen species (mtROS), ATP, and cardiolipin, which activate the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. NLRP3 inflammasome is an important innate immune system element contributing to neuroinflammation and neurodegeneration. Therefore, targeting the NLRP3 inflammasome has become an interesting therapeutic approach for treating neurodegenerative diseases. This review describes the role of mitochondrial abnormalities and over-activated inflammasomes in the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Friedrich ataxia (FRDA). We also discuss the therapeutic strategies focusing on signaling pathways associated with inflammasome activation, which potentially alleviate neurodegenerative symptoms and impede disease progression.